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In this presentation,
more suitable for larger particles suitable for wide range of particle sizes -micro
and millimeter range
With the two methods, different distributions are obtained unless particles are
truly spherical
Generally, laser diffraction preferred but according to USP <786> sieve analysis
may be used if at least 80% of particles are shown to have size larger than 75m
Test site 1, 10 15 19
Therefore,
- Routine testing procedure should be applied consistently as was used for the biolot
API batch- to reduce factors that contribute to variations, e.g. sample preparation
steps should be applied consistently
- Results from another site can not be relied upon unless adequately validated based
experience on several batches to ensure minimal variations (as part of vendor
qualification)
If the difference between the two batches is significant: we can take the average values
11
WHO PREQUALIFICATION TEAM
Polymorph ID test- some times also required
in the FPP specifications
In most cases, polymorph ID test in the FPP is not required. However,
when
- thermodynamic unstable form is used
- the FPP manufacturing process involves change of the API form, for
example from crystalline to amorphous form,
- Both APIs should be controlled for PSD at the time of release (and when multiple
forms are identified then for polymorph ID as well)
- Critically insoluble APIs should also be tested for PSD at the time of retesting and
during stability studies (and when multiple forms are identified then for polymorph
ID as well)
Sima R, Fathollah F. Experimental studies on the effects of process parameters on granule properties in a conical high shear
granulator. Iran J. Chem. Eng. Vol 32, No. 3, 2013
Wet granulation: Yes Spray rate, atomization air - Processing using exact same parameters
FBD processor pressure, inlet temp, exhaust as was used for biobatch or as validated
- requires 15-30% temp - Measuring exhaust temp, product temp
granulating fluid and drying time
Melt extrusion No Feeder speed, melt/zone - Processing using exact same parameters
temperature, melt pressure as was used for biobatch or as validated
Dry granulation: No Roll gap, roller pressure, roller - Processing using exact same parameters
Compaction speed, horizontal and vertical as was used for biobatch or as validated
screw feed speed, number of
compaction cycle
See hand out 3 for the applicants response (revised blank BMR)
Ideally batch processing is completed within 30 days from the first date
on which the API is mixed with excipients
With this study, the individual hold times and cumulative hold time of 180 days are justified
- Shelf life for the FPP remains 24 months